Phase I trial of docetaxel and thalidomide: a regimen based on metronomic therapeutic principles

Invest New Drugs. 2008 Aug;26(4):355-62. doi: 10.1007/s10637-008-9137-0. Epub 2008 May 10.

Abstract

Purpose: Pre-clinical models have demonstrated the benefit of metronomic schedules of cytotoxic chemotherapy combined with anti-angiogenic compounds. This trial was undertaken to determine the toxicity of a low dose regimen using docetaxel and thalidomide.

Patients and methods: Patients with advanced solid tumors were enrolled. Thalidomide 100mg twice daily was given with escalating doses of docetaxel from 10 to 30 mg/m(2)/week. One cycle consisted of 12 consecutive weeks of therapy. The maximal tolerated dose (MTD) was defined as the dose of thalidomide along with docetaxel that caused < or =grade 1 non-hematologic or < or =grade 2 hematologic toxicity for cycle one.

Results: Twenty-six patients were enrolled. Dose-limiting toxicities (DLTs) were bradycardia, fatigue, fever, hyperbilirubinemia, leukopenia, myocardial infarction, and neutropenia. Prolonged freedom from disease progression was observed in 44.4% of the evaluable patients.

Conclusions: This anti-angiogenic regimen was well tolerated and demonstrated clinical benefit. The recommended phase II dosing schedule is thalidomide 100 mg twice daily with docetaxel 25 mg/m(2)/week.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / physiopathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / physiopathology
  • Paclitaxel / administration & dosage
  • Thalidomide / administration & dosage

Substances

  • Angiogenesis Inhibitors
  • Thalidomide
  • Paclitaxel